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EP1413321B1 - Phosphathaltiger Knochenersatzwerkstoff mit kristallinen und röntgenamorphen Phasen - Google Patents

Phosphathaltiger Knochenersatzwerkstoff mit kristallinen und röntgenamorphen Phasen Download PDF

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Publication number
EP1413321B1
EP1413321B1 EP03090348A EP03090348A EP1413321B1 EP 1413321 B1 EP1413321 B1 EP 1413321B1 EP 03090348 A EP03090348 A EP 03090348A EP 03090348 A EP03090348 A EP 03090348A EP 1413321 B1 EP1413321 B1 EP 1413321B1
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EP
European Patent Office
Prior art keywords
weight
bone replacement
sio
mgo
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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EP03090348A
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German (de)
English (en)
French (fr)
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EP1413321A3 (de
EP1413321A2 (de
Inventor
Georg Berger
Andrea Spitzer
Christian Prof. Jäger
Jutta Pauli
Renate Gildenhaar
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Bundesanstalt fuer Materialforschung und Pruefung BAM
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Bundesanstalt fuer Materialforschung und Pruefung BAM
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Publication of EP1413321A3 publication Critical patent/EP1413321A3/de
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    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C3/00—Glass compositions
    • C03C3/12—Silica-free oxide glass compositions
    • C03C3/16—Silica-free oxide glass compositions containing phosphorus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C3/00—Glass compositions
    • C03C3/04—Glass compositions containing silica
    • C03C3/062—Glass compositions containing silica with less than 40% silica by weight
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the invention relates to a high solubility X-ray amorphous crystalline material useful both as a bioactive bone substitute material, e.g. as a coating of metallic prosthetic stems by thermal spraying, by RF sputtering, as well as a substrate material in biotechnology, especially tissue engineering, e.g. also as a ceramic film, as a compact or porous, i. Spongiosa-like, "scaffold" -like, moldings can be applied.
  • tissue engineering e.g. also as a ceramic film, as a compact or porous, i. Spongiosa-like, "scaffold" -like, moldings can be applied.
  • the invention also relates to a production method.
  • Inorganic materials with high absorbability are known per se. Even materials that find their specific use as bioactive bone replacement materials and have a fast solubility are described in the literature. For example, alpha or beta tricalcium phosphate (TCP) has been consistently reported on the successful clinical use of ceramics with the main crystal phases. In addition, there have also been comparative studies of these two TCP phases in animal studies. It is known from EP 237043 that dicalcium phosphate is present on the surface of granules produced from alpha-TCP, which had a higher solubility, especially in the initial phase after implantation, than the pure core material of alpha-TCP.
  • TCP tricalcium phosphate
  • bioactive materials based on calcium phosphates which additionally contain oxides of potassium, sodium, magnesium and / or silicon (EP 541546 B1) and their glassy crystalline material is based on the following main crystal phases phase X, rhenanite, phase according to Ando (phase A) or derived from these previously mentioned phases mixed crystals.
  • WO 91/07357 discloses oxide compositions which can be used as a bone substitute material with rapid solubility, consisting of a crystalline X phase and, depending on the melting range, other phases containing CaO, Na 2 O, K 2 O, MgO, P 2 O 5 , SiO 2 and optionally sulfates.
  • the composition is sintered or melted and thereafter cooled appropriately, depending on the desired crystal phase, to give solubilities in the range of 3-15 mg / g become.
  • DE 19744809 C discloses a glassy-crystalline glass body with Ca-K-Na-phosphate main crystal phases having rapid solubility as a bone replacement material prepared by fusing together two glasses, one of the glasses containing 20-55% CaO, 5-25 Na 2 O, O, 01-20 K 2 O, 0-15 MgO, 30-50 P 2 O 5 and 0-15 SiO 2 .
  • the porosity is obtained by leaching the borosilicate glass phase to a residual of 0.05-2% by weight.
  • US-A-3922155 discloses a process for producing biocompatible glass-ceramics which comprises melting a SiO 2 , Na 2 O, K 2 O, MgO, CaO and Ca 3 (PO 4) 2 mixture and further ceramization steps.
  • BIOMATERIALS Vol. 18, No. 20 (1997) 1339-1347 describes the use of Ca 2 KNa (PO 4 ) 2 as bone substitute material, but without information on production and phases.
  • the object of the invention is to provide an X-ray amorphous-crystalline material which enables a predominantly direct, connective tissue-free bone composite or ex vivo cultivation of bone cells and which dissolves in contact with bone tissue and thereby improves adjustable high solubilities and at the same time in composites has certain coefficients of expansion adapted to certain steels.
  • Another object is to develop a manufacturing process for the material and auxiliaries for the production.
  • the diphosphates are preferred in the secondary crystal phase, but can also include one or more of the substances NaPO 3, be KPO 3 and mixtures containing thereof, wherein the chain phosphates NaPO 3 and KPO 3 to 31 P-NMR measurements are demonstrated as Q 2 -groups ,
  • the proportion of chain phosphates is 0.1 to 10% by weight, preferably 0.1 to 4% by weight.
  • a silicate phase may be present in a proportion of up to 6% by weight.
  • magnesium may be present up to a proportion of 10% by weight, calculated as MgO and based on the weight of the finished material.
  • the proportion of the orthophosphate phase as Q 0 groups may preferably be in the range of 75 to 99% by weight, in particular in the range of 78 to 95% by weight.
  • the proportion of the diphosphate phase as Q 1 groups may preferably be in the range from 1 to 22% by weight, in particular in the range from 5 to 16% by weight.
  • composition of the high solubility X-ray amorphous crystalline material based on CaO, P 2 O 5 , Na 2 O, K 2 O, MgO and possibly also SiO 2 is in the range of (in% by weight): 30 to 55 P 2 O 5; 25 to 50 CaO; 1 to 20 Na 2 O; 0.5 to 20 K 2 O; 0 to 13 MgO; 0 to 10 SiO 2 ; wherein MgO or SiO 2 or a mixture thereof is at least 1% by weight.
  • a preferred X-ray amorphous crystalline material contains the following constituents: in% by weight: 35 to 48 P 2 O 5 , 28 to 38 CaO, 2.5 to 15 Na 2 O, 1.5 to 18 K 2 O, 0.1 to 4 MgO, 0.0 to 3 SiO 2 .
  • a specific preferred embodiment contains 40 to 52 P 2 O 5 , 28 to 33 CaO, 8.5 to 13 Na 2 O, 9.5 to 15 K 2 O, 1.5 to 3 MgO, 0.1 to 4 SiO 2 ,
  • X-ray amorphous-crystalline material used here is generally not clearly definable.
  • X-ray amorphous is here understood to mean a material whose structure can no longer be detected with the usual XRD (X-ray diffractometry). These can be very small ordered areas (microcrystalline) as well as statistically disordered areas.
  • XRD X-ray diffractometry
  • the existence of each crystalline phase can be detected by the 31 P NMR results. Therefore, the quantity estimation between NMR and XRD results can lead to significant differences.
  • the diphosphate and chain phosphate components seem to be symptomatic in this case for this phenomenon; As a rule, significantly higher fractions are determined with the 31 P NMR measurements than with XRD. In some cases, no shares are even determined with XRD. This astonishingly shows why the 31 P-NMR measurements for the characterization and ultimately production of the materials according to the invention form an essential prerequisite.
  • the XRD measurements were made with a PW 1710, Philipps, NL (Cu
  • main crystal phase refers to a crystalline phase determined by X-ray diffraction, the proportion of which is at least twice that of a minor phase, concentrations of 20% and below, preferably below 15% by weight, being referred to as secondary phases.
  • the 31 P NMR measurements which were carried out with a superconducting Fourier NMR spectrometer Avance DMX400 WB from Bruker BioSpin GmbH (Germany), showed that the material consists of 70 to 99.9% by weight of orthophosphate, formed from calcium and, optionally, sodium, potassium and magnesium, said orthophosphate portion being detected by 31 P-NMR measurements on Q 0 groups and relating to crystalline and / or X-ray amorphous material in its entirety.
  • 0.1 to 30% by weight of diphosphate were found, formed from calcium and possibly sodium, potassium and magnesium, this diphosphate content demonstrably by 31 P-NMR measurements (Q 1 groups) and refers to crystalline and / or X-ray amorphous material in its entirety.
  • the Diphosphatanteile result from a comparatively high phosphate content compared to the other components. This could also be causally responsible for the fact that the compositions according to the invention melt very easily in comparison to known resorbable materials and give a thin liquid melt. Such a liquid melt has the advantage that it is easier to process. This is e.g. on a frit of the melt or on a direct blowing of the melt, etc. too.
  • the material (the X-ray amorphous-crystalline material) changes its ion discharge in the direction of physiological pH values (7.4) after initially strongly alkaline reaction in comparison to materials, which contain no diphosphate.
  • This pH value shift also makes the material interesting for biotechnology and tissue engineering.
  • This feature can be reinforced by leaching a molded article (compact or open-pore) on the surface by boiling in deionized water (37-90 ° C.), so that the material or shaped article treated in this way becomes leached after this treatment has significantly lower pH values. The reason for this could be considered a depletion of the alkaline cations in the near-surface region.
  • This process can be accelerated by boiling in a reactor, advantageously under a pressure of up to 10 bar. Such an embodiment of the invention is preferred.
  • the material according to the invention is prepared by the substances suitable for the batch formation in the concentration range (based on the total weight of the material) 30-55% by weight CaO, 35-50% by weight P 2 O 5 , 1-20% by weight Na 2 O, 0.5-20% by weight of K 2 O and 0.1-5% by weight of MgO and optionally up to 5% by weight of SiO 2 are combined, and in multi-stage temperature treatment programs with holding levels in the range of 200 to 1500 ° C. for 1-2 hours at 350 - 400 ° C, 750 - 850 ° C and 950 - 1050 ° C, for example, each 1h at 400, 800 and 1000 ° C in a suitable crucible material, eg. B.
  • a suitable crucible material eg. B.
  • melts consisting of a Pt / Rh alloy, are melted at 1550 to 1650 ° C.
  • the melt is, preferably after a holding time of 10 to 60 minutes, potted, and the solidified melt is cooled depending on the intended use in the air (spontaneous cooling) or in the cooling furnace with temperature programmed cooling of eg 1 to 20 degrees / min to room temperature. It can also be blown, resulting in spherical granules directly from the melt flow. During the cooling of the melts always a spontaneous crystallization takes place.
  • As batch constituents it is possible to use oxides, carbonates, hydrogen phosphates and / or ortho-phosphoric acid.
  • the 31 P NMR measurements show differences in the spectra, which allow conclusions to be drawn on the raw materials used or indicate their slight admixtures of iron or manganese oxides.
  • Preferred melting temperatures are 1590-1650 ° C.
  • the material After cooling, the material is granulated and used as bone substitute material, but it can, for example, also ground, mixed with conventional sintering aids and then isostatically pressed into moldings to give after sintering as close as possible fired ceramic cullet.
  • the sintering temperatures are generally 900 to 1200 ° C.
  • a portion of the raw materials used is melted separately in order to produce a glass which acts as a sintering aid and can be used for the cancellous bone-like moldings with particular advantage.
  • This likewise ground glass can be added to the slurry, which consists of the material according to the invention, which was previously ground after melting and cooling and then was acidified.
  • the separately melted glass may be added in an amount of 0.5-15%, preferably 4-8% by weight, so that however the individual components do not exceed the compositional specifications according to the invention.
  • Such a glass can be formed in particular on the basis of SiO 2 , MgO and Na 2 O.
  • the separately molten glass has a grain size D 50 of 0.7 to 7 ⁇ m, the material having approximately the same or a larger grain size.
  • Another processing option is to mill up the material, to add conventional sintering aids and to process the slip thus obtained into a film which exhibits an open-pore structure after the firing process.
  • the material according to the invention can also be present in combination with a metallic implant surface.
  • the coefficient of expansion is in the range of 12 to 18x10 -6 K -1 , measured by means of dilatometer (silica glass pushrod dilatometer, Netzsch, Germany), an adaptation to known steels, such as chromium-cobalt-molybdenum steels with similar expansion coefficient, particularly advantageous.
  • the batches were weighed as follows: code CaCO 3 in g MgO in g 85% H 3 PO 4 in ml Na 2 CO 3 in g K 2 CO 3 in g SiO 2 in g GA 1 54,74 2.45 41.48 16,11 21,01 0 GA 2 53.40 2.39 42.82 15.72 20.50 0 GA 3 52.13 2.33 44.09 15.34 20.01 0
  • the components of calcium, magnesium, sodium and potassium, possibly also silicon are weighed. After weighing, mix each batch in a tumble mixer for one hour. Thereafter, the mixture is mixed with the 85% ortho-phosphoric acid, well ground and stirred and dried for one hour at 100 ° C, mortared again and again stored for one hour at 100 ° C in a drying oven. The mixture was then resorbed and filled into a Pt / Rh shell and heated to 400 ° C, held at this temperature for one hour after reaching this temperature, then heated to 800 ° C, after reaching this temperature again for one hour at kept this temperature and then heated to 1000 ° C and held for one hour after reaching this temperature at this temperature.
  • This sinter cake was cooled in air and mortared again for the purpose of homogenization.
  • This pretreated batch was then filled into a platinum crucible and heated in the furnace to 1600 ° C. After reaching this temperature, the melt was left for half an hour at this temperature.
  • the low-viscosity homogeneous melts were then poured onto a steel plate and pressed with another steel plate to a salt-like solidified plate. The resulting crystallization gives the enamel bodies an opaque, white color.
  • a further production possibility consists inter alia in that the entire amount of phosphorus or phosphate or, as in the present example, a part can be introduced through a calcium carrier.
  • the following composition was synthesized according to the specifications in% by weight: code CaO MgO P 2 O 5 Na 2 O K 2 O SiO 2 GA 1 30.67 2:45 43.14 9.42 14.32 0.00
  • the mixture was weighed in accordance with this specification, mixed for one hour in a tumble mixer, mixed with the phosphoric acid, dried for one hour at 100 ° C, cooled in air and mortared.
  • This batch was placed in a platinum crucible and filled into a 450 ° C preheated oven and held for 6 hours, then placed in an oven preheated to 800 ° C and held at that temperature for 16 hours.
  • the crucible was removed and the oven is now preheated to 950 ° C. In the oven preheated to 950 ° C, the crucible was held for 6 hours. The sample was then heated to 1600 ° C and held at this temperature half an hour after reaching this temperature.
  • the thin homogeneous melt was then poured onto a steel plate and pressed with another steel plate to a salt-like solidified plate.
  • the resulting crystallization gives the enamel bodies an opaque, white color.
  • discoloration can be observed.
  • the result with the specified range for the composition GA 1 relates to a total of three batches, one batch being synthesized according to the production method mentioned in Example 3.
  • PUR sponges open porosity polyurethane
  • the sintering aid used was 3% by weight of a previously prepared glass having the chemical composition in mass% SiO 2 : 74.97; MgO: 9.22 and Na 2 O: 15.81 (melted in as 27.04 Na 2 CO 3 ) and a D 50 of 6.56 ⁇ m were added to the millbase of GA 1. 100 g of this powder mixture were mixed with 45 g of a mixture consisting of 90% polyethylene glycol and 10% of a commercial wetting agent with the addition of 5 ml isopropyl alcohol to a slurry.
  • This slurry is applied to PUR open porosity sponges of 31.49-7.87 pores / cm (80 to 20 ppi pores per inch) by repeated dipping and squeezing, dried in an oven overnight at 120 ° C and then slowly with 10 ° C per minute to 1000 ° C heated.
  • a spongiosa-like material with the starting sponge similar structure is present, and the PUR sponge burned out without residue.
  • FIGS. 1 and 2 respectively show in the left (broad) peak, the Q 0 -groups and in the right-hand (smaller) peak, the Q 1 groups.
  • Material of the composition with the code designation GA 1 was freshly ground and 1 g of a fraction of ⁇ 45 ⁇ m were added to 100 ml of E-pure water and the pH was determined after 1 min and after 72 h. The result after one minute was 10.55 and after 72 hours 8.71, i. shifted significantly in the direction of physiological conditions.
  • the thermal expansion coefficient can be varied, considering, for example, that titanium implants are 8 ⁇ 10 -6 K -1 and Co-Cr-Mo steels by 14-16 • 10 -6 ⁇ K -1 (depending on the alloy constituents).
  • it plays a role in which temperature range of the material is applied to the metallic substrate, as well as targeted in this way the substrate through the coating under compressive stresses, ie under preheating can set what generally considered to be a more mechanically stable composite.
  • AK 30-100 means the expansion coefficient between 30 and 100 ° C
  • AK RT ** 400 is the expansion coefficient between room temperature (25) and 400 ° C
  • AK 50-400 is the expansion coefficient between 50 and 400 ° C.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Geochemistry & Mineralogy (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Materials Engineering (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Surgery (AREA)
  • Materials For Medical Uses (AREA)
EP03090348A 2002-10-21 2003-10-16 Phosphathaltiger Knochenersatzwerkstoff mit kristallinen und röntgenamorphen Phasen Expired - Lifetime EP1413321B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10249627A DE10249627B4 (de) 2002-10-21 2002-10-21 Knochenersatzwerkstoff mit kristallinen und amorphen Phasen und Verfahren zu seiner Herstellung sowie seine Verwendung
DE10249627 2002-10-21

Publications (3)

Publication Number Publication Date
EP1413321A2 EP1413321A2 (de) 2004-04-28
EP1413321A3 EP1413321A3 (de) 2004-07-14
EP1413321B1 true EP1413321B1 (de) 2006-01-04

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EP03090348A Expired - Lifetime EP1413321B1 (de) 2002-10-21 2003-10-16 Phosphathaltiger Knochenersatzwerkstoff mit kristallinen und röntgenamorphen Phasen

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US (2) US7547448B2 (da)
EP (1) EP1413321B1 (da)
AT (1) ATE314867T1 (da)
DE (2) DE10249627B4 (da)
DK (1) DK1413321T3 (da)
ES (1) ES2256670T3 (da)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10249626B4 (de) * 2002-10-21 2005-07-07 BAM Bundesanstalt für Materialforschung und -prüfung Knochenersatzwerkstoff mit kristallinen und Glasphasen und Verfahren zu seiner Herstellung sowie seine Verwendung
DE10307646B3 (de) * 2003-02-21 2004-10-21 Ivoclar Vivadent Ag Bioaktive Rhenanit-Glaskeramik, Verfahren zu ihrer Herstellung und ihre Verwendung
DE102009000642B4 (de) 2009-02-05 2012-12-06 BAM Bundesanstalt für Materialforschung und -prüfung Verfahren zur Herstellung mikrostrukturierter Bauteile mittels Photolithographie
CN101905036A (zh) * 2009-06-04 2010-12-08 佳木斯大学 一种新型羟基磷灰石/SiOC生物陶瓷复合材料及其制备方法
CN101612420B (zh) * 2009-08-13 2013-01-09 湖南大学 多量纳米网状碳-羟基磷灰石复合材料及其制备方法
EP2529764A1 (de) * 2011-05-31 2012-12-05 Curasan AG Biologisch degradierbares kompositmaterial

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* Cited by examiner, † Cited by third party
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BE815374A (fr) * 1973-05-23 1974-09-16 Matiere vitroceramique et procede pour la preparer
DD258713A3 (de) 1986-03-14 1988-08-03 Akad Wissenschaften Ddr Calciumphosphathaltiger, biokompatibler schichtkoerper und verfahren zu seiner herstellung
DD302011A9 (de) * 1989-11-13 1994-11-03 Biovision Gmbh Entwicklung Glasiges oder glasig-kristallines Material mit schneller Loeslichkeit und Verfahren zu seiner Herstellung
US6117456A (en) * 1995-05-19 2000-09-12 Etex Corporation Methods and products related to the physical conversion of reactive amorphous calcium phosphate
DE19744809C1 (de) * 1997-10-02 1999-07-01 Georg Dr Berger Poröser, glasig-kristalliner Formkörper mit schneller Löslichkeit, Verfahren zu seiner Herstellung und Verwendung
DE10249625B4 (de) * 2002-10-21 2005-08-04 BAM Bundesanstalt für Materialforschung und -prüfung Pulvergemisch für resorbierbare Calciumphosphat-Biozemente und ihre Verwendung

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US20040228927A1 (en) 2004-11-18
DE10249627A1 (de) 2004-05-06
US20090197972A1 (en) 2009-08-06
DE10249627B4 (de) 2005-07-21
US8182832B2 (en) 2012-05-22
US7547448B2 (en) 2009-06-16
EP1413321A3 (de) 2004-07-14
ATE314867T1 (de) 2006-02-15
DK1413321T3 (da) 2006-05-22
EP1413321A2 (de) 2004-04-28
ES2256670T3 (es) 2006-07-16
DE50302115D1 (de) 2006-03-30

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